JP2005120023A - Skin care preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation having truly excellent bleaching effect with no problems in terms of stability, safety, smell, etc. <P>SOLUTION: The skin care preparation contains an L-ascorbic acid 2-O-alkyl ether derivative and one or more ingredients selected from the group consisting of L-ascorbic acid and its salt, an L-ascorbic acid ester derivative and its salt, an L-ascorbic acid glycoside and its salt, an alkoxysalicylic acid and its salt, a hydroquinone glycoside and its salt, tranexamic acid and its derivative, a resorcinol derivative, kojic acid, ellagic acid, linoleic acid and chamomile extract. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an external preparation for skin. More specifically, the present invention relates to a highly safe external skin preparation with significantly improved skin whitening effect.

  Although there are unclear points about the mechanism of skin spots, freckles, etc., melanin pigments are generally formed due to hormonal abnormalities such as MSH and female hormones and the stimulation of ultraviolet rays from sunlight. It is thought to be abnormally deposited in the skin.

  Therefore, for the treatment of such stains and freckles, a substance that suppresses the production of melanin, for example, a method of administering L-ascorbic acid in a large amount, or kojic acid, cysteine, etc. in the form of an ointment, cream, lotion, etc. For example, it is applied locally.

In addition, L-ascorbic acid 2-O-alkyl ether derivatives are disclosed in a technique for blending into a skin external preparation useful for whitening (see Patent Document 1). Furthermore, the technique mix | blended with cosmetics as an antioxidant is disclosed (refer patent document 2).
However, many of these have problems in terms of stability, safety, odor and the like, and the expected effects are weak and still not satisfactory.

Japanese Patent Laid-Open No. 62-221611 JP-A-1-228978

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a skin external preparation having a truly excellent whitening effect and having no problems in terms of stability, safety, odor and the like.

  As a result of intensive studies to solve the above problems, the present inventors have synergistically whitened the whitening effect when a 2-O-alkyl ether derivative of L-ascorbic acid and a conventionally known specific whitening agent are used in combination. It has been found that the above problems can be solved by increasing, and the present invention has been completed.

  That is, the present invention relates to L-ascorbic acid and salts thereof, ester derivatives of L-ascorbic acid and salts thereof, glycosides and salts of L-ascorbic acid, alkoxysalicylic acid and salts thereof, glycosides of hydroquinone and One or more selected from the group consisting of salts, tranexamic acid and derivatives thereof, derivatives of resorcinol, kojic acid, ellagic acid, linoleic acid, and chamomile extract, and 2-O-alkyl ether of L-ascorbic acid It is a skin external preparation characterized by containing a derivative.

  According to the present invention, L-ascorbic acid and a salt thereof, an ester derivative of L-ascorbic acid and a salt thereof, a glycoside of L-ascorbic acid and a salt thereof, an alkoxysalicylic acid and a salt thereof, a glycoside of hydroquinone and a salt thereof One or more selected from the group consisting of salts, tranexamic acid and derivatives thereof, derivatives of resorcinol, kojic acid, ellagic acid, linoleic acid, chamomile extract, and 2-O-alkyl ether derivatives of L-ascorbic acid Therefore, it is possible to obtain a highly safe topical skin preparation with significantly improved skin whitening effect.

Hereinafter, preferred embodiments of the present invention will be described.
The topical skin preparation of the present invention includes L-ascorbic acid 2-O-alkyl ether derivatives, L-ascorbic acid and salts thereof, ester derivatives of L-ascorbic acid and salts thereof, and glycosides of L-ascorbic acid And salts thereof, alkoxysalicylic acid and salts thereof, glycosides of hydroquinone and salts thereof, tranexamic acid and derivatives thereof, derivatives of resorcinol, kojic acid, ellagic acid, linoleic acid, and chamomile extract Or 2 or more types are contained.

  The L-ascorbic acid and its salt, the ester derivative of L-ascorbic acid and its salt, and the glycoside of L-ascorbic acid and its salt used in the present invention will be described.

  L-ascorbic acid used in the present invention is generally referred to as vitamin C, and is known to have a cell respiration action, an enzyme activation action, a collagen formation action due to its strong reduction action, and a melanin reduction action.

  In addition, the salt used for the L-ascorbate used in the present invention is not particularly limited. For example, an alkali metal salt or alkaline earth metal salt such as sodium salt, potassium salt, magnesium salt, calcium salt is used. Other salts include ammonium salts and amino acid salts. Specific examples of L-ascorbate include sodium L-ascorbate. One or more L-ascorbates are arbitrarily selected and blended.

  Examples of L-ascorbic acid ester derivatives and salts thereof used in the present invention include L-ascorbic acid monostearate, L-ascorbic acid monopalmitate, L-ascorbic acid monooleate, L-ascorbic acid distearate, L-ascorbic acid alkyl esters such as L-ascorbic acid dipalmitate and L-ascorbic acid diolate; L-ascorbic acid phosphoric acid ester, L-ascorbic acid phosphoric acid magnesium salt, L-ascorbic acid phosphoric acid sodium salt, etc. -Ascorbic acid phosphate and its salt; L-ascorbic acid-2-sulfate such as L-ascorbic acid-2-sulfate, L-ascorbic acid-2-sulfate, magnesium salt and the like it canOf these salts, various salts including those exemplified above can be used.

  Examples of the salt that can be formed include salts such as ammonium salts and amino acid salts in addition to alkali metal salts or alkaline earth metal salts such as sodium salts, potassium salts, magnesium salts, and calcium salts. Salts can be prepared by known methods. In addition, in the case of a salt of L-ascorbic acid phosphate, an alkaline earth metal salt, particularly a magnesium salt is preferable.

  Moreover, as a glycoside of L-ascorbic acid used in this invention, and its salt, L-ascorbic acid glucoside which makes a suitable example L-ascorbic acid 2-glucoside etc. can be mentioned, for example.

  The alkoxysalicylic acid and its salt used in the present invention will be described.

  Alkoxysalicylic acid used in the present invention is a known substance, and a hydrogen atom at any of the 3-position, 4-position or 5-position of salicylic acid is substituted with an alkoxy group. Preferred examples of the alkoxy group as the substituent include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, and an isobutoxy group. A methoxy group or an ethoxy group is particularly preferable.

As an example of a specific compound name of alkoxysalicylic acid,
2-hydroxy-3-methoxybenzoic acid,
2-hydroxy-3-ethoxybenzoic acid,
4-methoxysalicylic acid (2-hydroxy-4-methoxybenzoic acid),
2-ethoxy-4-ethoxybenzoic acid,
4-propoxysalicylic acid (2-hydroxy-4-propoxybenzoic acid),
4-isopropoxysalicylic acid (2-hydroxy-4-isopropoxybenzoic acid),
4-butoxysalicylic acid (2-hydroxy-4-butoxybenzoic acid),
2-hydroxy-5-methoxybenzoic acid,
2-hydroxy-5-ethoxybenzoic acid,
2-Hydroxy-5-propoxybenzoic acid
Etc. In the present invention, 4-methoxysalicylic acid is particularly preferable.

  In order to obtain alkoxysalicylic acid, for example, 5-methoxysalicylic acid can be easily synthesized by the method described in Beil, 10227, and 4-methoxysalicylic acid can be synthesized by Beil, 10379. Moreover, it is commercially available as a reagent from Aldrich, etc., and it is also possible to use it.

  The alkoxysalicylic acid can be made into a salt by a known method, but alkoxysalicylic acid may be added in the form of a salt to the external preparation for skin of the present invention.

  A preferred salt is 4-methoxysalicylate. Although it does not specifically limit as said salt, For example, salts, such as ammonium salt and an amino acid salt other than alkali metal salt or alkaline-earth metal salt like sodium salt, potassium salt, calcium salt, are mentioned. In the present invention, potassium salts are preferable, and potassium 4-methoxysalicylate is particularly preferable. One or more alkoxysalicylic acids and salts thereof are arbitrarily selected and blended.

  The hydroquinone glycoside and its salt used in the present invention will be described.

  The hydroquinone glycoside used in the present invention is a known substance, for example, hydroquinone α-D-glucose, hydroquinone β-D-glucose, hydroquinone α-L-glucose, hydroquinone β-L-glucose, hydroquinone α- Hexasaccharide glycosides such as D-galactose, hydroquinone β-D-galactose, hydroquinone α-L-galactose, hydroquinone β-L-galactose, hydroquinone α-D-ribose, hydroquinone β-D-ribose, hydroquinone α- Pentose glycosides such as L-ribose, hydroquinone β-L-ribose, hydroquinone α-D-arabinose, hydroquinone β-D-arabinose, hydroquinone α-L-arabinose, hydroquinone β-L-arabinose, hydroquinone α- D -Glucosamine, hydroquinone β-D-glucosamine, hydroquinone α-L-glucosamine, hydroquinone β-L-glucosamine, hydroquinone α-D-galactosamine, hydroquinone β-D-galactosamine, hydroquinone α-L-galactosamine, hydroquinone β-L- Amino sugar glycosides such as galactosamine, hydroquinone α-D-glucuronic acid, hydroquinone β-D-glucuronic acid, hydroquinone α-L-glucuronic acid, hydroquinone β-L-glucuronic acid, hydroquinone α-D-galacturonic acid, hydroquinone Examples include uronic acid glycosides such as β-D-galacturonic acid, hydroquinone α-L-galacturonic acid, and hydroquinone β-L-galacturonic acid.

  In the present invention, the hydroquinone glycoside is preferably hydroquinone β-D-glucose and / or hydroquinone α-D-glucose. In particular, the use of hydroquinone β-D-glucose (generic name: arbutin, hereinafter referred to as arbutin) is preferable in terms of whitening effect, availability, and stability. One or more hydroquinone glycosides and salts thereof are arbitrarily selected and blended.

  The tranexamic acid and its derivative used in the present invention will be described.

  Tranexamic acid used in the present invention is a known substance, and examples of the tranexamic acid derivative include amides of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salt, trans-4- (P- Methoxybenzoyl) aminomethylcyclohexanecarboxylic acid and its salts), dimer of tranexamic acid [trans-4- (trans-aminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid, etc.] hydrochloride, ester of tranexamic acid and hydroquinone ( Trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester, etc.), ester of tranexamic acid and gentisic acid [2- (trans-4-aminomethylcyclohexylcarbonyloxy)- - hydroxybenzoic acid and its salts, trans-4-guanidinomethyl cyclohexane carboxylic acid and salts thereof.

  In the present invention, among tranexamic acid and derivatives thereof, tranexamic acid and tranexamic acid methylamide hydrochloride are preferable. One or more tranexamic acids and derivatives thereof are arbitrarily selected and blended.

  The derivative of resorcinol used in the present invention will be described.

  A typical example of the resorcinol derivative used in the present invention is alkylresorcinol. Specifically, 4-alkylresorcinol is preferable, and 4-n-butylresorcinol is more preferable. One or more resorcinol derivatives are arbitrarily selected and blended.

  Kojic acid, ellagic acid and linoleic acid used in the present invention are known substances.

  The chamomile extract used in the present invention will be described.

  The chamomile extract used in the present invention is a known substance, such as chamomile [Matricaria chamomilla L. (Compositae)] is an extract obtained by extracting a flower with a solvent. Examples of the extraction solvent include water, hydrophilic organic solvents such as methanol, ethanol, propanol, propylene glycol, and 1,3-butylene glycol, nonpolar oils such as squalene, and mixed solvents thereof. Such chamomile extract generally contains camazulene, umbelliferone, 7-methoxycoumarin, matricin, matricalin, taraxasterol, lupeol, and apiin.

  As a specific method for extracting chamomile, for example, a chamomile flower is dried, an ethanol / water mixed solvent is added to the chopped flower, and it is immersed at room temperature to 50 ° C. with occasional stirring. The extract is obtained by squeezing the test.

  In the present invention, an extract extracted from chamomile flowers with a solvent can be used as it is, but an arbitrary amount of the solvent may be removed and concentrated to be used as an extract concentrate. Moreover, it can also be used after adding operations, such as deodorizing and refine | purifying, in the range which does not impair the effect of this invention. Moreover, it can also be used as a dried product by removing the solvent from these, and the dried product may be used by dissolving it in a solvent at an arbitrary concentration. Further, a fraction may be obtained by using column chromatography or the like. The chamomile extract in the present invention can be used in any form such as an extract, an extract concentrate, a deodorized product, a purified product, a dried product, a dried product solution, and a fraction. Commercially available products can be used for the chamomile extract of the present invention, and examples of commercially available products include “Kamitele Liquid” (manufactured by Ichimaru Falcos Co., Ltd., solid content: 0.60 to 1.20% by mass). .

  L-ascorbic acid and salts thereof, ester derivatives of L-ascorbic acid and salts thereof, glycosides of L-ascorbic acid and salts thereof, alkoxysalicylic acid and salts thereof, and hydroquinone One or two or more compounding amounts selected from the group consisting of saccharides and salts thereof, tranexamic acid and derivatives thereof, derivatives of resorcinol, kojic acid, ellagic acid, linoleic acid, and chamomile extract are the total amount of the external preparation for skin. The content is preferably 0.001 to 20% by mass. If the blending amount is less than 0.001% by mass, the skin whitening effect of the external preparation for the skin tends to be poor, and conversely, even if it exceeds 20% by mass, an increase in the effect is practically not expected. Blending also tends to be difficult. A more preferable blending amount is 0.01 to 10% by mass, particularly preferably 0.1 to 7% by mass. The chamomile extract is an amount converted to a dry product.

  The skin external preparation of the present invention further contains a 2-O-alkyl ether derivative of L-ascorbic acid.

  The 2-O-alkyl ether derivative of L-ascorbic acid used in the present invention is a known substance, and is described in, for example, JP-A-62-221611. Examples of 2-O-alkyl ether derivatives of L-ascorbic acid include 2-O-methyl-L-ascorbic acid, 2-O-ethyl-L-ascorbic acid, 2-O-n-propyl-L-ascorbine. Acid, 2-O-isopropyl-L-ascorbic acid, 2-O-n-butyl-L-ascorbic acid, 2-O-isobutyl-L-ascorbic acid, 2-O-tert-butyl-L-ascorbic acid, 2-On-pentyl-L-ascorbic acid, 2-On-hexyl-L-ascorbic acid, 2-On-heptyl-L-ascorbic acid, 2-On-octyl-L-ascorbic acid Acid, 2-On-nonyl-L-ascorbic acid and the like. One or two or more kinds of 2-O-alkyl ether derivatives of L-ascorbic acid are arbitrarily selected and blended, and 2-O-methyl-L-ascorbic acid and 2-O-ethyl exemplified above are included. -L-ascorbic acid, 2-On-propyl-L-ascorbic acid, 2-O-isopropyl-L-ascorbic acid, 2-On-butyl-L-ascorbic acid, 2-O-isobutyl-L -It is preferable that 1 type (s) or 2 or more types chosen from the group which consists of ascorbic acid and 2-O-tert- butyl-L-ascorbic acid are mix | blended.

  As for the compounding quantity of the 2-O-alkyl ether derivative of L-ascorbic acid mix | blended with the skin external preparation of this invention, 0.001-20 mass% is preferable in the skin external preparation whole quantity. If the blending amount is less than 0.001% by mass, the whitening effect of the external preparation for skin and the effect of suppressing the skin irritation of the external preparation for skin tend to be poor. The increase is virtually undesired, and it tends to be difficult to formulate into a topical skin preparation. A more preferable blending amount is 0.01 to 7% by mass.

  In addition to the above-described essential components, the external preparation for skin of the present invention is usually used for other external preparations for skin, such as cosmetics and pharmaceuticals, such as oils, surfactants, thickeners, wetting agents, moisturizing agents. An agent, an ultraviolet absorber, an antioxidant, an antiseptic, a fragrance, water, alcohol, and the like can be appropriately blended as necessary within a range not impairing the effects of the present invention.

  The dosage form of the external preparation for skin according to the present invention is arbitrary, and for example, any dosage form such as a solubilizing system such as lotion, an emulsifying system such as emulsion or cream, or an ointment or dispersion can be taken. .

  The external preparation for skin of the present invention refers to an external preparation applied to the outer skin as a cosmetic, pharmaceutical, or quasi-drug, for example, ointment, cream, emulsion, lotion, essence, jelly, gel, pack, mask, bath It is used as an agent.

Hereinafter, the present invention will be described in more detail with reference to examples. In addition, this invention is not limited by this. A compounding quantity is the mass%. Prior to the examples, an effect test method will be described.

[In vitro whitening effect test]
(Test method)
A cell homogenate obtained by adding extraction buffer (100 mM phosphate buffer (pH 7.4), 150 mM NaCl, 1% Triton X-100) to cultured B16 melanoma cells was centrifuged at 12,000 rpm for 10 minutes, and the supernatant was obtained as a crude enzyme. Used as a liquid. The crude enzyme solution and DOPA are mixed in 100 mM phosphate buffer to a final concentration of 10% by mass and 1 mM, respectively, and the test sample is mixed so as to have the drug compounding amount (% by mass) shown in Tables 1 to 5 and cultured at 37 ° C. did. Visibility determination of the degree of blackening after 60 minutes was performed. In addition, the chamomile extract in a table | surface is an ethanol / water (8/2; mass ratio) extract (a compounding quantity is a dry matter conversion amount).

Table 6 shows the determination results. The criteria for determination are as follows.
(Criteria)
-: No change relative to the degree of blackening of the control without drug.
±: Slightly blackened.
+: Slightly blackened.
++: Blackening was considerably suppressed.
+++: Blackening was completely suppressed.

表６より明らかなように、Ｌ−アスコルビン酸リン酸エステルマグネシウム塩、４−メトキシサリチル酸カリウム、コウジ酸、アルブチン、トラネキサム酸、エラグ酸、４−ｎ−ブチルレゾルシノール、リノール酸及びカミツレエキスに、２−Ｏ−メチルアスコルビン酸、２−Ｏ−エチルアスコルビン酸、２−Ｏ−ｎ−プロピルアスコルビン酸及び２−Ｏ−ｎ−ブチルアスコルビン酸をそれぞれ併用した試験試料（皮膚外用剤）は、相乗的に優れた黒化抑制効果を発揮することが認められた。

As is apparent from Table 6, L-ascorbic acid phosphate magnesium salt, potassium 4-methoxysalicylate, kojic acid, arbutin, tranexamic acid, ellagic acid, 4-n-butylresorcinol, linoleic acid and chamomile extract -O-methyl ascorbic acid, 2-O-ethyl ascorbic acid, 2-O-n-propyl ascorbic acid and 2-O-n-butyl ascorbic acid are used in combination with each other. It was recognized that it exhibited an excellent blackening suppression effect.

[Whitening effect test by in vivo]
(Test method)
One test sample (lotion) was applied to the face every day for 3 months in the morning and evening, and the whitening effect was examined 3 months later. The formulation of the lotion (skin external preparation) used in the test is shown below. In addition, the chamomile extract in a table | surface is an ethanol / water (8/2; mass ratio) extract (a compounding quantity is a dry matter conversion amount). Production was in accordance with conventional methods.

(Test sample (lotion) prescription)
Ingredient Amount (% by mass)
(Alcohol phase)
95% ethyl alcohol 25.0
Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0
Preservative / Antioxidant Appropriate amount of perfume Appropriate amount of agent (described in Tables 7 to 9) Amounts described in Tables 7 to 9 (aqueous phase)
Glycerin 2.0
Propylene glycol 1.0
Ion exchange water

Table 10 shows the effect test results (whitening effect). The determination criteria and determination were performed as follows.
(Criteria)
Remarkable: Pigmentation is almost inconspicuous.
Effective: The pigmentation became very faint.
Slightly effective: Pigmentation became slightly faint.
Invalid: No change.

(Judgment)
(Double-circle): When the ratio (effective rate) which shows remarkable and effective among test subjects is 80% or more.
◯: When the ratio (effective rate) showing remarkable and effective among test subjects is 50% or more and less than 80%.
Δ: When the ratio (effective rate) of the test subject showing remarkable and effective is 30% or more and less than 50%.
X: When the ratio (effective rate) which shows remarkable and effective among test subjects is less than 30%.

    As is apparent from Table 10, L-ascorbic acid phosphate magnesium salt, potassium 4-methoxysalicylate, kojic acid, arbutin, tranexamic acid, ellagic acid, 4-n-butylresorcinol, linoleic acid and chamomile extract It was confirmed that the test sample (skin external preparation) in which -O-methylascorbic acid and 2-O-ethylascorbic acid were used in combination synergistically exhibited an excellent skin whitening effect.

  Hereinafter, the formulation example of this invention external preparation for skin is shown. In addition, when the above effect tests were performed on these, excellent whitening effects were recognized in all cases.

"Prescription Example 1 Vanishing Cream"
Ingredient Amount (% by mass)
Stearic acid 5.0
Stearyl alcohol 4.0
Stearic acid butyl alcohol ester 8.0
Glycerin monostearate ester 2.0
L-ascorbic acid distearate 1.0
Propylene glycol 10.0
2-O-methylascorbic acid 0.1
Preservative / Antioxidant Appropriate amount of perfume Appropriate amount of ion-exchanged water

(Manufacturing method)
Propylene glycol and 2-O-methylascorbic acid were added to ion-exchanged water and dissolved, and heated to 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase, and after the addition was completed, the temperature was maintained for a while to cause the reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

"Prescription Example 2 Vanishing Cream"
Ingredient Amount (% by mass)
Stearic acid 6.0
Sorbitan monostearate ester 2.0
Polyoxyethylene (20 mol) sorbitan monostearate
1.5
Arbutin 7.0
Propylene glycol 10.0
2-O-ethylascorbic acid 1.0
Preservative / Antioxidant Appropriate amount of perfume Appropriate amount of ion-exchanged water

(Manufacturing method)
Arbutin, propylene glycol and 2-O-ethylascorbic acid were added to ion-exchanged water and heated to 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

"Prescription example 3 neutral cream"
Ingredient Amount (% by mass)
Stearyl alcohol 7.0
Stearic acid 2.0
Hydrogenated Lanolin 2.0
Squalane 5.0
2-Octilde Deserial Call 6.0
Polyoxyethylene (25 mol) cetyl alcohol ether 3.0
Glycerin monostearate ester 2.0
Hydroquinone α-D-glucose 0.1
Propylene glycol 5.0
2-O-n-propylascorbic acid 7.0
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of ion-exchanged water

(Manufacturing method)
Hydroquinone α-D-glucose, propylene glycol and 2-On-propylascorbic acid were added to ion-exchanged water and heated to 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

"Prescription Example 4 Cold Cream"
Ingredient Amount (% by mass)
Solid paraffin 5.0
Honey wax 10.0
Vaseline 15.0
Liquid paraffin 41.0
Glycerin monostearate ester 2.0
Polyoxyethylene (20 mol) sorbitan monolaurate
2.0
Kojic acid 1.0
Soap powder 0.1
Borax 0.2
2-O-n-butylascorbic acid 0.01
Ion-exchanged water Residual fragrance Appropriate amount Preservative / Antioxidant Appropriate amount

(Manufacturing method)
Kojic acid, soap powder, borax and 2-On-butylascorbic acid were added to ion-exchanged water, dissolved by heating and kept at 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The reaction was gradually added while stirring the oil phase in the aqueous phase. After completion of the reaction, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well after emulsification.

"Prescription Example 5 Latex"
Ingredient Amount (% by mass)
Polyoxyethylene (20 mol) Polyoxypropylene (2 mol) Cetyl alcohol 1.0
Silicone KF96 (20cs) (manufactured by Shin-Etsu Chemical Co., Ltd.) 2.0
Liquid paraffin (medium viscosity) 3.0
Propylene glycol 5.0
4-n-butylresorcinol 2.0
Glycerin 2.0
Ethyl alcohol 15.0
Carboxyvinyl polymer 0.3
Hydroxypropyl cellulose 0.1
2-Aminomethylpropanol 0.1
Preservative appropriate amount 2-O-methylascorbic acid 0.5
Ion exchange water

(Manufacturing method)
4-n-Butyl resorcinol was heated and dissolved in ion-exchanged water and ethanol, and further water-soluble components below propylene glycol were dissolved and kept at 70 ° C. (aqueous phase). Other oil components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well.

“Prescription Example 6 Latex”
Ingredient Amount (% by mass)
Polyoxyethylene (20 mol) Polyoxypropylene (2 mol) Cetyl alcohol 1.0
Silicone KF96 (20cs) (manufactured by Shin-Etsu Chemical Co., Ltd.) 2.0
Liquid paraffin (medium viscosity) 3.0
Propylene glycol 5.0
L-ascorbic acid-2-sulfate sodium salt 5.0
Glycerin 2.0
Ethyl alcohol 15.0
Carboxyvinyl polymer 0.3
Hydroxypropyl cellulose 0.1
2-Aminomethylpropanol 0.1
Preservative appropriate amount 2-O-ethylascorbic acid 0.5
Ion exchange water

(Manufacturing method)
Water-soluble components below propylene glycol were dissolved in ion-exchanged water and ethanol and kept at 70 ° C. (aqueous phase). Other oil components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well.

"Prescription Example 7 Latex"
Ingredient Amount (% by mass)
Polyoxyethylene (20 mol) Polyoxypropylene (2 mol) Cetyl alcohol
1.0
Silicone KF96 (20cs) (manufactured by Shin-Etsu Chemical Co., Ltd.) 2.0
Liquid paraffin (medium viscosity) 3.0
Propylene glycol 5.0
Glycerin 2.0
Ethyl alcohol 15.0
Carboxyvinyl polymer 0.3
Hydroxypropyl cellulose 0.1
2-Aminomethylpropanol 0.1
Preservative appropriate amount L-ascorbic acid-2-glucoside 2.0
2-O-ethylascorbic acid 0.5
Ion exchange water

(Manufacturing method)
L-ascorbic acid-2-glucoside was heated and dissolved in ion-exchanged water and ethanol, and further water-soluble components below propylene glycol were dissolved and kept at 70 ° C. (aqueous phase). Other oil components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well.

"Prescription Example 8 Latex"
Ingredient Amount (% by mass)
Polyoxyethylene (20 mol) Polyoxypropylene (2 mol) Cetyl alcohol 1.0
Silicone KF96 (20cs) (manufactured by Shin-Etsu Chemical Co., Ltd.) 2.0
Liquid paraffin (medium viscosity) 3.0
Propylene glycol 5.0
Glycerin 2.0
Ethyl alcohol 15.0
Carboxyvinyl polymer 0.3
Hydroxypropyl cellulose 0.1
2-Aminomethylpropanol 0.1
Preservative appropriate amount L-ascorbic acid-2-glucoside 2.0
2-O-methylascorbic acid 1.0
Ion exchange water

(Manufacturing method)
L-ascorbic acid-2-glucoside was heated and dissolved in ion-exchanged water and ethanol, and further water-soluble components below propylene glycol were dissolved and kept at 70 ° C. (aqueous phase). Other oil components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well.

"Prescription Example 9 Latex"
Ingredient Amount (% by mass)
Stearic acid 1.5
Cetyl alcohol 0.5
Honey wax 2.0
Chamomile extract (ethanol-extracted dried product) 1.0
Polyoxyethylene (20 mol) monooleate 1.0
Glycerin monostearate ester 1.0
Quince seed extract (5% aqueous solution) 20.0
Ethyl alcohol 10.0
Tranexamic acid 2.0
Propylene glycol 5.0
2-O-ethylascorbic acid 0.5
Ion-exchanged water Residual fragrance Appropriate amount Preservative / Antioxidant Appropriate amount

(Manufacturing method)
Tranexamic acid, propylene glycol and 2-O-ethylascorbic acid were added to ion-exchanged water, dissolved by heating and kept at 70 ° C. (aqueous phase). Perfume was added to ethyl alcohol and dissolved (alcohol phase). The other components except the quince seed extract were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer. While stirring this, the alcohol phase and the quince seed extract were added. Thereafter, the mixture was cooled to 30 ° C. while stirring.

"Prescription Example 10 Latex"
Ingredient Amount (% by mass)
Microcrystalline wax 1.0
Honey wax 2.0
Lanolin 2.0
Liquid paraffin 20.0
Squalane 10.0
Sorbitan sesquioleate ester 4.0
Polyoxyethylene (20 mol) sorbitan monooleate
1.0
Linoleic acid 2.0
Kojic acid 2.0
Propylene glycol 7.0
2-On-butyl ascorbic acid 2.0
Ion-exchanged water Residual fragrance Appropriate amount Preservative / Antioxidant Appropriate amount

(Manufacturing method)
Linoleic acid, kojic acid, propylene glycol and 2-On-butylascorbic acid were added to ion-exchanged water and heated to maintain at 70 ° C. (aqueous phase). The other components were mixed, dissolved by heating and kept at 70 ° C. (oil phase). While stirring the oil phase, the water phase was gradually added to this oil phase and uniformly emulsified with a homomixer. It cooled to 30 degreeC, stirring well after emulsification.

"Prescription Example 11 Jelly"
Ingredient Amount (% by mass)
95% ethyl alcohol 10.0
Dipropylene glycol 15.0
Polyoxyethylene (15 mol) oleyl alcohol ether 2.0
Potassium 4-methoxysalicylate 0.5
L-ascorbic acid-2-glucoside 0.5
Carboxyvinyl polymer (trade name: Carbopol 941) 1.0
Caustic potash 0.15
L-Arginine 0.1
2-O-ethylascorbic acid 0.3
Perfume Appropriate amount Preservative Appropriate amount of ion-exchanged water Residual

(Manufacturing method)
L-ascorbic acid 2-glucoside, 4-methoxysalicylic acid potassium, 2-O-ethylascorbic acid and carbopol 941 are uniformly dissolved in ion-exchanged water, while dipropylene glycol, polyoxyethylene (15 mol) in 95% ethanol. ) Oleyl alcohol ether and other ingredients were dissolved and added to the aqueous phase. Next, the mixture was neutralized with caustic potash and L-arginine to increase the viscosity.

"Prescription Example 12: Peel-off type pack"
Ingredient Amount (% by mass)
(Alcohol phase)
95% ethanol 10.0
Polyoxyethylene (15 mol) oleyl alcohol ether 2.0
2-O-ethylascorbic acid 7.0
Preservative Appropriate amount Perfume Appropriate amount
Glutathione 3.0
Arbutin 3.0
Polyvinyl alcohol 12.0
Polyethylene glycol 1500 1.0
Ion exchange water

(Manufacturing method)
An aqueous phase was prepared at 80 ° C and cooled to 50 ° C. Subsequently, after adding the alcohol phase prepared at room temperature, it mixed uniformly and allowed to cool.

"Prescription Example 13 Pack with powder"
Ingredient Amount (% by mass)
(Alcohol phase)
95% ethanol 2.0
2-O-ethylascorbic acid 1.0
Preservative Appropriate amount of perfume Appropriate amount of colorant Appropriate amount of L-ascorbic acid dioleate 1.0
(Water phase)
Arbutin 3.0
Propylene glycol 7.0
Zinc flower 25.0
Kaolin 20.0
Ion exchange water

(Manufacturing method)
The aqueous phase was uniformly prepared at room temperature. Subsequently, the alcohol phase prepared at room temperature was added and mixed uniformly.

“Prescription Example 14: Water-absorbing ointment”
Ingredient Amount (% by mass)
Vaseline 40.0
Stearyl alcohol 18.0
Owl 20.0
Polyoxyethylene (10 mol) monooleate 0.25
Glycerin monostearate 0.25
Ellagic acid 1.0
2-O-n-butylascorbic acid 1.0
Ion exchange water

(Manufacturing method)
Ellagic acid and 2-On-butylascorbic acid were added to ion-exchanged water and kept at 70 ° C. (aqueous phase). Other components were mixed and dissolved at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer and then cooled.

“Formulation Example 15 Moisturizing Gel”
Ingredient Amount (% by mass)
Glycerin 7.0
Polyethylene glycol (PEG1500) 8.0
Agar 2.0
2-O-ethylascorbic acid 0.01
L-ascorbic acid phosphate magnesium salt 1.0
Tranexamic acid 2.0
Citric acid Appropriate amount Sodium citrate Appropriate amount Sodium hydroxide Appropriate amount of purified water Residual phenoxyethanol Appropriate amount HEDTA3Na Appropriate perfume Appropriate amount

(Manufacturing method)
Agar, xanthan gum and 2-O-ethylascorbic acid were added to purified water and dissolved at 90 ° C. This was cooled to 50 ° C., the remaining components were added, and further cooled to 30 ° C. or less to be gelled. When sufficiently hardened, the gel was crushed using a disper to form a microgel (average particle size 70 μm), and then degassed to obtain a moisturizing gel. The amounts of citric acid, sodium citrate, and sodium hydroxide were appropriately adjusted so that the pH of the system was 7.

  Hereinafter, the external preparation for skin of the present invention was further produced by a conventional method.

"Prescription Example 16 Essence"
Ingredient Amount (% by mass)
Liquid paraffin 3.0
Vaseline 1.0
Methyl polysiloxane 1.0
Stearyl alcohol 2.0
Behenyl alcohol 3.0
Glycerin 8.0
Dipropylene glycol 5.0
Macadamia nut oil 2.0
Hardened oil 3.0
Squalane 6.0
Stearic acid 2.0
Cholesteryl hydroxystearate 0.5
Cetyl 2-ethylhexanoate 4.0
Polyoxyethylene (20) behenyl ether 1.0
Potassium hydroxide appropriate amount Sodium hexametaphosphate appropriate amount 2-O-ethylascorbic acid 0.1
Tranexamic acid 1.0
Trimethylglycine 2.0
DL-α-tocopherol 2-L-ascorbic acid phosphate diester potassium 1.0
DL-α-tocopherol acetate 0.1
Green tea extract 0.1
Paraben appropriate amount edetate trisodium appropriate amount 4-t-butyl-4'-methoxydibenzoylmethane 0.05
Diparamethoxycinnamate mono-2-ethylhexanoate glyceryl 0.05
Bengala appropriate amount yellow iron oxide appropriate amount carboxyvinyl polymer 0.1
Purified water residue

“Prescription Example 17 Cream”
Ingredient Amount (% by mass)
Liquid paraffin 8.0
Vaseline 3.0
Methylpolysiloxane 2.0
Stearyl alcohol 3.0
Behenyl alcohol 2.0
Glycerin 5.0
Dipropylene glycol 4.0
Trehalose 1.0
2-O-methylascorbic acid 2.0
L-ascorbyl-2-glucoside 2.0
Tetra-2-ethylhexanoic acid pentaerythrit 4.0
Polyoxyethylene glyceryl isostearate 2.0
Polyoxyethylene glyceryl monostearate 1.0
Lipophilic glyceryl monostearate 2.0
1,1'-methylene-bis (4-isocyanatocyclohexane) polyfluoroethylene glycol copolymer 1.0
Citric acid 0.05
Sodium citrate 0.05
Potassium hydroxide 0.015
Licorice flavonoids 0.1
Retinol acetate (1.5 million units) 0.2
DL-α-tocopherol acetate 0.1
Paraoxybenzoic acid ester Appropriate amount Phenoxyethanol Appropriate amount Dibutylhydroxytoluene 0.1
Edetate trisodium 0.05
4-t-butyl-4′-methoxydibenzoylmethane 0.01
2-Ethylhexyl paramethoxycinnamate 0.1
β-carotene 0.01
Polyvinyl alcohol 0.5
Hydroxyethyl cellulose 0.5
Carboxyvinyl polymer 0.05
Purified water Residual fragrance Appropriate amount

"Prescription Example 18 Essence"
Ingredient Amount (% by mass)
Vaseline 2.0
Methylpolysiloxane 2.0
Ethyl alcohol 5.0
Behenyl alcohol 0.5
Batyl alcohol 0.2
Glycerin 7.0
1,3-butylene glycol 5.0
Polyethylene glycol 20000 0.5
Jojoba oil 3.0
Squalane 2.0
Tetra-2-ethylhexanoic acid pentaerythrit 1.0
Polyoxyethylene hydrogenated castor oil 1.0
Potassium hydroxide 0.1
Sodium pyrosulfite appropriate amount sodium hexametaphosphate appropriate amount stearyl glycyrrhetinate 0.1
Pantothenyl ethyl ether 0.1
2-O-n-propylascorbic acid 1.0
Arbutin 7.0
L-ascorbic acid sodium salt 2.0
Tocopherol acetate 0.1
Acetylated sodium hyaluronate 0.05
Paraoxybenzoic acid ester appropriate amount edetate trisodium appropriate amount 4-t-butyl-4'-methoxydibenzoylmethane 0.1
Diparamethoxycinnamic acid mono-2-ethylhexanoate glyceryl 0.1
Yellow iron oxide xanthane gum 0.1
Carboxyvinyl polymer 0.2
Purified water residue

"Prescription Example 19 Cream"
Ingredient Amount (% by mass)
Methylpolysiloxane 3.0
Decamethylcyclopentasiloxane 4.0
Ethyl alcohol 5.0
Glycerin 6.0
1,3-butylene glycol 5.0
Polyoxyethylene methyl glucoside 3.0
Sunflower oil 1.0
Squalane 2.0
Potassium hydroxide 0.1
Sodium hexametaphosphate appropriate amount 2-O-ethylascorbic acid 0.5
4-methoxysalicylate potassium 1.0
Hydroxypropyl-β-cyclodextrin 0.1
Dipotassium glycyrrhizinate 0.05
Loquat leaf extract 0.1
Sodium L-glutamate 0.05
Fennel extract 0.1
Lavender oil 0.1
Giant extract 0.1
Paraben proper amount dimorpholinopyridazinone 0.1
Bengala appropriate amount yellow iron oxide appropriate amount xanthan gum 0.1
Carboxyvinyl polymer 0.1
Acrylic acid / alkyl methacrylate copolymer 0.1
Purified water residue

“Prescription Example 20 Cream”
Ingredient Amount (% by mass)
1,3-butylene glycol 2.0
Dipropylene glycol 1.0
Glycerin 2.0
Adecanol GT-700 (Asahi Denka Kogyo) 2.0
Pemulen TR-2 (Goodrich) 0.2
Decamethylcyclopentasiloxane 2.0
Squalane 1.0
2-O-ethylascorbic acid 4.0
Arbutin 3.0
Vitamin E acetate 0.5
4-methoxysalicylate potassium 1.0
Potassium hydroxide appropriate amount citric acid 0.02
Sodium citrate 0.08
EDTA3Na 0.02
Sodium pyrosulfite 0.03
Methylparaben 0.15
Phenoxyethanol 0.1
1,2-pentanediol 0.1
Dye appropriate amount ethanol 5.0
Ion exchange water

“Prescription Example 21 Cream”
Ingredient Amount (% by mass)
Methylpolysiloxane 3.0
Cyclomethicone 25.0
Polyoxyethylene / methylpolysiloxane copolymer 2.0
Glycerin 1.0
1,3-butylene glycol 5.0
Squalane 1.0
Titanium oxide 1.0
Talc 2.0
2-O-ethylascorbic acid 0.7
Tranexamic acid 2.0
EDTA3Na appropriate amount paraben appropriate amount phenoxyethanol appropriate amount sodium pyrosulfite appropriate amount dimethyl distearyl ammonium hectorite 0.8
Spherical nylon powder 1.0
Purified water residue

"Prescription Example 22 Lotion"
Ingredient Amount (% by mass)
Ethyl alcohol 10.0
Dipropylene glycol 1.0
Polyethylene glycol 1000 1.0
Polyoxyethylene methyl glucoside 1.0
Jojoba oil 0.01
Glyceryl tri-2-ethylhexanoate 0.1
Polyoxyethylene hydrogenated castor oil 0.2
Polyglyceryl diisostearate 0.15
N-stearoyl-L-glutamate sodium 0.1
Citric acid 0.05
Sodium citrate 0.2
Potassium hydroxide 0.4
Dipotassium glycyrrhizinate 0.1
Arginine hydrochloride 0.1
2-O-ethylascorbic acid 0.5
L-ascorbic acid-2-glucoside 2.0
Ogon Extract 0.1
Yukinoshita extract 0.1
Paraben appropriate amount Odorikosou extract 0.1
Dibutylhydroxytoluene 0.01
Edetate trisodium appropriate amount 2-methoxyhexyl paramethoxycinnamate 0.01
Purified water Residual mineral water 3.0
Perfume

“Prescription Example 23 Mask”
Ingredient Amount (% by mass)
Ethanol 3.0
Glycerin 12.0
Sorbit liquid (70%) 15.0
Titanium oxide 0.35
Dry aluminum hydroxide gel 0.1
2-O-ethylascorbic acid 2.0
Arbutin 3.0
P-Hydroxybenzoate 0.15
Fish gelatin 0.1
Sodium polyacrylate 6.5
Sodium carboxymethylcellulose 2.0
Carboxyvinyl polymer 1.0
Purified water Residual fragrance Appropriate amount

Claims (8)

L-ascorbic acid and salts thereof, ester derivatives of L-ascorbic acid and salts thereof, glycosides and salts of L-ascorbic acid, alkoxysalicylic acid and salts thereof, glycosides and salts of hydroquinone, tranexamic acid and salts thereof A derivative, a derivative of resorcinol, kojic acid, ellagic acid, linoleic acid, and one or more selected from the group consisting of chamomile extract, and a 2-O-alkyl ether derivative of L-ascorbic acid An external preparation for skin. 2-O-alkyl ether derivatives of L-ascorbic acid are 2-O-methyl-L-ascorbic acid, 2-O-ethyl-L-ascorbic acid, 2-On-propyl-L-ascorbic acid, 2 -O-isopropyl-L-ascorbic acid, 2-O-n-butyl-L-ascorbic acid, 2-O-isobutyl-L-ascorbic acid, and 2-O-tert-butyl-L-ascorbic acid Item 1. An external preparation for skin according to Item 1. The ester derivative of L-ascorbic acid and its salt were selected from the group consisting of L-ascorbic acid alkyl ester and its salt, L-ascorbic acid phosphate and its salt, and L-ascorbic acid sulfate and its salt The external preparation for skin according to claim 1 or 2, wherein the external preparation is one or more. The skin according to any one of claims 1 to 3, wherein the glycoside of L-ascorbic acid and a salt thereof are one or more selected from the group consisting of L-ascorbic acid glucoside and a salt thereof. Topical agent. The skin external preparation according to any one of claims 1 to 4, wherein the alkoxysalicylic acid and a salt thereof are 4-methoxysalicylic acid and a salt thereof. The skin external preparation according to any one of claims 1 to 5, wherein the glycoside of hydroquinone and a salt thereof are hydroquinone β-D-glucose and / or hydroquinone α-D-glucose. The skin external preparation according to any one of claims 1 to 6, wherein tranexamic acid and its derivative are tranexamic acid and / or tranexamic acid methylamide hydrochloride. The skin external preparation according to any one of claims 1 to 7, wherein the derivative of resorcinol is 4-n-butylresorcin.